{
  "id": "myelodysplastic-syndrome",
  "title": "Myelodysplastic Syndrome",
  "lang": "en",
  "source_lang": "en",
  "summary": "A group of clonal bone marrow cancers characterized by ineffective blood-cell production, cytopenias, and a variable risk of acute myeloid leukemia.",
  "category": "health",
  "subcategory": "diseases",
  "type": "concept",
  "aliases": [
    "MDS",
    "myelodysplastic syndromes",
    "myelodysplastic neoplasm",
    "myelodysplastic neoplasms"
  ],
  "generated_at": "2026-10-22",
  "model": "pro/gpt-6.1-sol",
  "url": "https://aiwiki.page/en/myelodysplastic-syndrome/",
  "translations": {
    "zh-Hans": {
      "url": "https://aiwiki.page/zh/myelodysplastic-syndrome/",
      "json": "https://aiwiki.page/zh/myelodysplastic-syndrome.json"
    }
  },
  "sections": [
    {
      "heading": "",
      "text": "Myelodysplastic syndrome (MDS) denotes a heterogeneous group of cancers arising in blood-forming stem and progenitor cells of the bone marrow. Abnormal maturation and ineffective blood-cell production cause persistent shortages of circulating red blood cells, white blood cells, or platelets, despite a marrow that is often rich in cells. MDS is itself a malignancy, not simply a precancerous condition, although some cases progress to acute myeloid leukemia. The fifth edition of the World Health Organization classification introduced the name “myelodysplastic neoplasms,” retaining the abbreviation MDS. (nature.com)\n\nThe disorders vary substantially in their genetic abnormalities, clinical course, and treatment requirements. Their consequences include anemia, infection, bleeding, and impaired quality of life. Diagnosis integrates blood counts, marrow examination, chromosome studies, and molecular testing; prognostic systems estimate risks beyond the diagnostic subtype. Treatment encompasses supportive care, medicines directed at particular disease features, and allogeneic hematopoietic stem cell transplantation, which offers the possibility of cure for selected patients. (cancer.gov)"
    },
    {
      "heading": "Terminology and Historical Development",
      "text": "MDS is a collective abbreviation for a heterogeneous group of clonal myeloid malignancies, traditionally called myelodysplastic syndromes. “Myeloid” refers here to the blood-forming compartment that produces red cells, granulocytes, monocytes, and platelets; “dysplastic” describes abnormalities of cellular development and appearance. These disorders combine ineffective hematopoiesis, persistent reductions in circulating blood cells, and characteristic marrow abnormalities. They are neoplasms—forms of cancer—rather than merely symptom-defined syndromes. Although some progress to acute myeloid leukemia (AML), transformation is not inevitable, and the designation does not mean that every patient is passing through a preliminary stage of leukemia. (pmc.ncbi.nlm.nih.gov)\n\nEarlier terminology reflected clinical observations made before these disorders could be defined genetically. In 1938, C. P. Rhoads and W. Halsey Barker published Refractory Anemia: Analysis of One Hundred Cases, examining severe anemia that had failed to respond to customary treatments, including liver extract or iron. “Refractory” therefore described resistance to the treatments then available, not a particular molecular lesion; this historical patient category should not be equated directly with modern MDS. Labels such as “preleukemia,” “smoldering leukemia,” and “dysmyelopoietic syndrome” subsequently emphasized either the observed association with leukemia or abnormal blood-cell production. (jamanetwork.com)\n\nA standardized morphological framework appeared in June 1982, when the French–American–British (FAB) Cooperative Group published its classification. The authors—J. M. Bennett, D. Catovsky, M. T. Daniel, G. Flandrin, D. A. G. Galton, H. R. Gralnick, and C. Sultan—defined five categories: refractory anemia; refractory anemia with ring sideroblasts; refractory anemia with excess blasts; chronic myelomonocytic leukemia; and refractory anemia with excess blasts “in transformation.” Classification relied chiefly on microscopic abnormalities in blood and bone marrow, including immature blast-cell proportions and iron-containing ring sideroblasts. This provided a common vocabulary for comparing patient groups and conducting clinical studies. (pubmed.ncbi.nlm.nih.gov)\n\nThe World Health Organization (WHO) classification published in 2001 began reorganizing this framework around integrated biological features. It recognized MDS with isolated deletion of chromosome 5q as a distinct entity, incorporating cytogenetic findings into disease definition. It also lowered the conventional AML blast threshold from 30% to 20%, eliminating the FAB “in transformation” category, and placed chronic myelomonocytic leukemia among disorders with overlapping myelodysplastic and myeloproliferative features. Consequently, historical FAB categories and later WHO categories do not describe identical patient populations. (haematologica.org)\n\nIn its fifth-edition framework introduced in 2022, WHO adopted “myelodysplastic neoplasms”, while retaining the abbreviation MDS, to make the neoplastic nature of the group explicit. It distinguished genetically defined entities involving isolated del(5q), SF3B1 mutation, or biallelic TP53 inactivation from entities defined predominantly by morphology. Classification thus increasingly combined cellular appearance with chromosome abnormalities and gene-level findings rather than replacing microscopy with genetics. The separate International Consensus Classification, also published in 2022, retained “myelodysplastic syndromes” while likewise integrating genomic information; the two names therefore coexist in classification systems and medical literature. (pmc.ncbi.nlm.nih.gov)"
    },
    {
      "heading": "Epidemiology and Predisposing Factors",
      "text": "MDS incidence rises steeply with age, particularly after the sixth decade. In the United States, the Surveillance, Epidemiology, and End Results (SEER) programme recorded 28,032 cases across 21 registry areas during 2013–2017. The annual incidence rate, age-adjusted to the 2000 US standard population using 19 age groups, was 4.3 per 100,000 people: 6.0 in males and 3.2 in females. Within the age bands reported by SEER, rates increased from 0.7 per 100,000 at ages 40–49 to 8.1 at 60–69, 26.3 at 70–79, and 54.2 at 80 years or older. The male excess was especially pronounced in the oldest group, with rates of 81.1 in males and 38.1 in females. These figures describe the participating registry populations during a specified historical period, rather than worldwide incidence. Childhood MDS is uncommon and has a different distribution of predisposing genetic disorders from adult disease. (seer.cancer.gov)\n\nMost patients have no identifiable external cause. Established predisposing exposures include previous cytotoxic chemotherapy, ionizing radiation—including radiotherapy—and benzene. Treatment-associated risk depends on the agents and exposure history; alkylating drugs and topoisomerase II inhibitors are important examples. Across secondary hematologic malignancies, typical intervals after alkylating agents or radiotherapy are approximately five to seven years, compared with two to three years after topoisomerase II inhibitors; these intervals are not fixed diagnostic boundaries or estimates specific to every MDS subtype. Occupational evidence also links benzene exposure to MDS: a 2012 international pooled analysis examined petroleum-distribution workers in Australia, Canada, and the United Kingdom, reconstructing exposure from historical monitoring records and assessing dose–response relationships. A population-level association does not establish that a particular exposure caused an individual patient’s disease, and the absence of recognized exposure does not exclude MDS. (cancer.gov)\n\nInherited predisposition results from a pathogenic germline variant present constitutionally, rather than solely within the abnormal blood-cell population. Such variants may be inherited or arise de novo. By contrast, acquired somatic mutations develop during life in individual cells and their descendants. The distinction cannot be made simply from the gene name: genes including RUNX1 and GATA2 can carry either germline or somatic alterations. Consequently, detecting a variant in blood or bone marrow does not by itself demonstrate hereditary disease. Germline predisposition also has variable penetrance: carrying a pathogenic variant increases susceptibility but does not mean that MDS inevitably develops. (cancer.gov)\n\nDDX41, GATA2, and RUNX1 illustrate distinct hereditary presentations. DDX41-associated myeloid neoplasms commonly present in later adulthood, so older age does not exclude inherited susceptibility. A 2022 cohort identified a median age of 69 years among patients with hematologic malignancies carrying causative germline DDX41 variants; concurrent acquired DDX41 variants were frequent. GATA2 deficiency can combine MDS susceptibility with immunodeficiency, recurrent infections, or lymphatic abnormalities. Germline GATA2 variants were identified in 7% of children with primary MDS in a European Working Group study cited by the National Cancer Institute. RUNX1-related familial platelet disorder may produce longstanding thrombocytopenia and impaired platelet function before MDS or acute myeloid leukemia develops. (pubmed.ncbi.nlm.nih.gov)\n\nInherited marrow-failure syndromes constitute another predisposing group. Fanconi anemia involves defective DNA repair, whereas Shwachman–Diamond syndrome involves abnormalities of ribosome biology; both increase susceptibility to MDS and acute myeloid leukemia. Telomere-biology disorders and severe congenital neutropenia are additional recognized settings. These disorders are particularly relevant to childhood and young-adult MDS, although constitutional predisposition can also become apparent later in life. Their underlying inherited defect is distinct from the additional somatic changes acquired as a myeloid neoplasm develops. (cancer.gov)"
    },
    {
      "heading": "Cellular and Molecular Pathogenesis",
      "text": "MDS develops through the expansion of abnormal hematopoietic stem cells whose descendants retain some capacity to produce blood cells but differentiate inefficiently. A clone can therefore gain a competitive advantage without generating adequate numbers of mature circulating cells. In 2014, Petter Woll and colleagues identified rare, disease-propagating stem cells in patient samples and traced acquired genetic abnormalities to this compartment. Impaired maturation and increased death of developing cells within the bone marrow produce ineffective hematopoiesis: cellular production does not translate into sufficient functional blood cells. Increased apoptosis contributes to this intramedullary loss, explaining how low peripheral blood counts can coexist with an actively populated marrow. The balance between stem-cell persistence, defective differentiation, and precursor-cell death varies among genetic forms of the disease. (pubmed.ncbi.nlm.nih.gov)\n\nRecurrent mutations affect several interacting biological pathways rather than a single disease-specific gene. In a 2013 study led by Elli Papaemmanuil, sequencing 111 genes in 738 patients with MDS or closely related myeloid neoplasms identified at least one oncogenic mutation in 78%; this figure describes that mixed cohort and assay, not all MDS populations. One major pathway is RNA splicing, which removes introns and joins exons in precursor messenger RNA. Mutant SF3B1 promotes use of abnormal splice sites. A 2016 study demonstrated aberrant splicing of ABCB7, producing a premature termination signal and degradation of its transcript; reduced ABCB7 expression provides a mechanism linking SF3B1 mutation to mitochondrial iron accumulation in ring sideroblasts. SRSF2 mutations instead alter recognition of RNA sequence motifs. Experimental work published in 2015 showed inclusion of a “poison” exon in EZH2, reducing this chromatin regulator’s expression and impairing hematopoietic differentiation. These are altered-function effects, not simply complete loss of splicing activity. (pmc.ncbi.nlm.nih.gov)\n\nA second group affects epigenetic regulation, changing gene activity without necessarily changing the sequence of downstream target genes. TET2 normally oxidizes methylated cytosine, whereas DNMT3A establishes DNA methylation. Experimental loss of either regulator can disturb the balance between stem-cell self-renewal and differentiation: Tet2-deficient mouse cells show enhanced repopulating capacity, while Dnmt3a-deficient stem cells progressively accumulate and lose differentiation capacity during serial transplantation. ASXL1 participates in chromatin regulation. Truncating ASXL1 mutations can alter histone modifications and transcriptional programs; mouse knock-in experiments demonstrated dysplastic hematopoiesis and cooperation with a RUNX1 mutation in leukemic transformation. Such findings establish functional effects but do not imply that any one mutation alone invariably produces human MDS. (pmc.ncbi.nlm.nih.gov)\n\nTranscriptional control and genome surveillance form another recurrently disrupted group. RUNX1 mutations interfere with programs required for blood-cell maturation; experimental human stem/progenitor-cell models demonstrate enhanced self-renewal and blocked myeloid differentiation. TP53 encodes a central regulator of cellular responses to DNA damage. Its allelic configuration matters: a 2020 study by Elsa Bernard and colleagues distinguished single-hit mutations from multi-hit states involving both gene copies, with the latter strongly associated with chromosomal instability. Successive acquisition or selection of mutations creates genetically distinct subclones. The 2013 sequencing study found that splicing and DNA-methylation abnormalities generally arose earlier than several signaling abnormalities, but mutation order was not uniform across patients. (pubmed.ncbi.nlm.nih.gov)\n\nThe abnormal clone also interacts with its marrow environment. Hind Medyouf and colleagues showed in 2014 that patient-derived MDS cells could reprogram mesenchymal stromal cells, creating a niche that supported disease propagation in transplantation models. Inflammatory signaling supplies another potential feedback mechanism. Ashley Basiorka and colleagues reported in 2016 that S100A9 and reactive oxygen species promoted NLRP3 inflammasome activation and pyroptosis, an inflammatory form of cell death, in patient specimens and experimental systems. This offers a mechanism by which inflammatory signals can simultaneously injure developing blood cells and reinforce abnormal clonal behavior. These studies support reciprocal clone–environment interactions, but neither stromal reprogramming nor NLRP3-mediated cell death is established as a universal initiating mechanism across all MDS subtypes. (pubmed.ncbi.nlm.nih.gov)"
    },
    {
      "heading": "Clinical Manifestations and Complications",
      "text": "Anemia commonly produces the most prominent symptoms: persistent fatigue, weakness, pallor, and shortness of breath, particularly during exertion. Reduced circulating hemoglobin lowers the blood’s oxygen-carrying capacity, so activities such as walking or climbing stairs may become disproportionately tiring. Symptoms can develop gradually, and some patients have no noticeable complaints when abnormal counts are first detected incidentally on a routine complete blood count. The clinical presentation therefore ranges from asymptomatic cytopenias to substantial limitations in ordinary activity; the presence or absence of symptoms alone does not establish the diagnosis. (cancer.gov)\n\nNeutropenia, a reduction in circulating neutrophils, weakens defense against infection. Abnormal leukocytes may also function poorly, meaning that infection susceptibility is not determined by the cell count alone. Infections can recur, require hospitalization, or progress to life-threatening sepsis. A 2024 report from the Düsseldorf MDS Registry found a significant association between increasing severity of neutropenia and infection; an absolute neutrophil count below 800 cells/µL was among the blood-count abnormalities associated with infectious complications. This observational association describes a study population rather than a universal threshold separating patients with and without infection risk. (pmc.ncbi.nlm.nih.gov)\n\nThrombocytopenia reduces the number of platelets available to maintain hemostasis, producing easy bruising, petechiae—small, pinpoint areas of bleeding beneath the skin—and mucosal bleeding. Platelet dysfunction adds a qualitative defect: circulating platelets may aggregate or release their granule contents abnormally even when their number is relatively preserved. In a clinicopathological study published in 2002, 48 patients with platelet counts above \\(80 \\times 10^{9}/\\mathrm{L}\\) underwent functional testing; only two had entirely normal results. Clinical hemorrhage occurred in 32 patients despite counts above \\(100 \\times 10^{9}/\\mathrm{L}\\). These findings demonstrate why the platelet count alone cannot fully describe bleeding susceptibility, although this selected cohort does not establish the frequency of hemorrhage across all MDS populations. (cancer.gov)\n\nPersistent anemia can lead to dependence on repeated red-cell transfusions. Although transfusions replace deficient cells and relieve anemia-related symptoms, repeated exposure introduces additional iron, which may accumulate in tissues and cause organ damage. Iron overload is therefore a complication of prolonged transfusion support rather than another manifestation of low blood counts. Recurrent infections and hemorrhage add separate burdens of acute illness, while transfusion dependence entails repeated healthcare encounters alongside the continuing effects of anemia. (cancer.gov)\n\nThe effects on quality of life extend beyond laboratory abnormalities. Fatigue and impaired physical functioning may restrict mobility and usual activities, while transfusion dependence contributes to the burden of living with the disease. A European MDS Registry study published in 2023 evaluated 2,205 patients during their first year after diagnosis. Hemoglobin below 10 g/dL and transfusion dependence were independently associated with poorer self-rated health, with adjusted odds ratios of 1.34 and 1.53, respectively. Comorbidity and reduced functional status were also important determinants, showing that symptom burden reflects both hematologic impairment and the patient’s broader health circumstances. (pubmed.ncbi.nlm.nih.gov)"
    },
    {
      "heading": "Diagnostic Investigation and Differential Diagnosis",
      "text": "Serial complete blood counts establish whether anemia, neutropenia, or thrombocytopenia is persistent and whether one or several cell lineages are affected. Differential counts quantify neutrophils and monocytes and identify circulating immature cells. Red-cell indices, particularly mean corpuscular volume, document macrocytosis, while the reticulocyte count assesses marrow red-cell output; MDS-associated anemia commonly has an inappropriately low reticulocyte response. Peripheral blood-film examination can reveal variation in red-cell size and shape, hypogranular neutrophils, abnormally hyposegmented neutrophil nuclei—the pseudo-Pelger–Huët anomaly—and unusually large or poorly granulated platelets. These findings support investigation but are not individually diagnostic. Previous counts, medication exposure, alcohol use, nutritional status, and concurrent illnesses help distinguish chronic unexplained cytopenias from transient or secondary abnormalities. (pmc.ncbi.nlm.nih.gov)\n\nBone marrow aspiration and a core biopsy provide complementary information. Aspirate smears permit assessment of erythroid, granulocytic, and megakaryocytic maturation and enumeration of blasts. Examples of dysplasia include abnormal nuclear segmentation in granulocytes and small, hypolobated megakaryocytes. The conventional morphological threshold is dysplasia in at least 10% of cells in an evaluated lineage, although qualifying genetic abnormalities can establish certain entities without this finding. An iron stain identifies ring sideroblasts: erythroid precursors containing at least five iron granules surrounding at least one-third of the nuclear circumference. The core biopsy assesses age-adjusted cellularity, tissue architecture, blast distribution, and reticulin or collagen fibrosis. Most MDS marrows are hypercellular despite low circulating counts, but hypocellular disease also occurs. (pmc.ncbi.nlm.nih.gov)\n\nConventional cytogenetic analysis detects chromosome gains, losses, and structural rearrangements, including del(5q), monosomy 7, and trisomy 8; approximately half of patients have a detectable cytogenetic abnormality. Fluorescence in situ hybridization examines selected chromosome regions and is particularly useful when metaphase preparations fail or an abnormality requires clarification, but its targeted probes do not replace a genome-wide karyotype. Targeted DNA sequencing detects somatic mutations and helps distinguish genetically defined entities. Neither a normal karyotype nor failure to detect a mutation excludes morphologically established MDS. Flow cytometry can demonstrate abnormal antigen-expression patterns across marrow cell populations and provide supportive evidence, but it does not independently establish the diagnosis. (cancer.gov)\n\nAn isolated age-associated mutation, such as one affecting DNMT3A or TET2, does not by itself establish MDS. The 2022 International Consensus Classification defines clonal hematopoiesis of indeterminate potential (CHIP) by a myeloid-neoplasm-associated somatic mutation with a variant allele frequency of at least 2%, or an appropriate non-MDS-defining clonal chromosome abnormality, without unexplained cytopenia or a myeloid neoplasm. Clonal cytopenia of undetermined significance (CCUS) combines clonality with otherwise unexplained cytopenia persisting for at least four months, without diagnostic dysplasia, increased blasts, or other criteria establishing a myeloid neoplasm. Thus, mutation detection must be interpreted alongside blood counts, morphology, and the specific genetic lesion. (pmc.ncbi.nlm.nih.gov)\n\nThe differential diagnosis includes vitamin B12 and folate deficiency, which can produce macrocytosis and abnormal marrow maturation, as well as copper deficiency, medication effects, alcohol-related changes, infection, and systemic disease. Copper deficiency can produce anemia, neutropenia, precursor-cell vacuolization, and ring sideroblasts; a 2002 report documented a patient previously considered to have sideroblastic MDS whose abnormalities were attributable to copper deficiency after gastric surgery. Hypocellular MDS must also be distinguished from aplastic anemia through integrated morphology, blast assessment, and genetic findings. Persistent monocytosis raises consideration of chronic myelomonocytic leukemia, whereas proliferative features or prominent fibrosis can indicate another myeloid neoplasm. Acute myeloid leukemia is distinguished using blast counts together with leukemia-defining genetic abnormalities, rather than a blast threshold alone. (pmc.ncbi.nlm.nih.gov)"
    },
    {
      "heading": "WHO and International Consensus Classification",
      "text": "The 2022 WHO fifth-edition classification recognizes three genetically defined MDS entities. MDS with low blasts and isolated 5q deletion (MDS-5q) requires fewer than 5% bone marrow blasts and fewer than 2% peripheral-blood blasts. Deletion of chromosome 5’s long arm may occur alone or with one additional cytogenetic abnormality, excluding monosomy 7 or del(7q). MDS with low blasts and SF3B1 mutation (MDS-SF3B1) has the same blast limits and excludes del(5q), monosomy 7, and complex karyotype. WHO uses an SF3B1 variant allele frequency—the proportion of sequencing reads carrying the variant—of at least 5%, compared with at least 10% in the International Consensus Classification (ICC). WHO also permits at least 15% ring sideroblasts to substitute for SF3B1 mutation, with the designation “MDS with low blasts and ring sideroblasts.” (pmc.ncbi.nlm.nih.gov)\n\nMDS with biallelic TP53 inactivation (MDS-biTP53) encompasses cases with fewer than 20% blasts in both marrow and blood. Qualifying findings are two or more TP53 mutations, or one mutation accompanied by TP53 copy-number loss or copy-neutral loss of heterozygosity, in which the remaining chromosomal copies derive from the same parental allele. A single TP53 mutation without evidence of a second hit does not establish this entity. Biallelic TP53 inactivation supersedes the MDS-5q and MDS-SF3B1 categories. (pmc.ncbi.nlm.nih.gov)\n\nWHO’s morphologically defined categories include MDS with low blasts (MDS-LB), with fewer than 5% marrow and fewer than 2% blood blasts, and hypoplastic MDS (MDS-h), with low blasts and age-adjusted marrow hypocellularity. MDS with increased blasts-1 (MDS-IB1) has 5–9% marrow or 2–4% blood blasts; MDS-IB2 has 10–19% marrow blasts, 5–19% blood blasts, or Auer rods. MDS with fibrosis (MDS-f) combines increased blasts—5–19% in marrow or 2–19% in blood—with significant marrow fibrosis, generally grade 2 or 3. ICC does not recognize separate hypoplastic or fibrotic MDS entities. (pmc.ncbi.nlm.nih.gov)\n\nThe ICC retains “myelodysplastic syndromes” and introduces MDS/AML for cytopenic myeloid neoplasms in adults with 10–19% marrow or blood blasts, unless AML-defining genetics dictate another diagnosis. Its MDS with excess blasts category instead covers 5–9% marrow or 2–9% blood blasts; 1% blood blasts documented twice also qualifies. ICC further excludes RUNX1 mutations and 3q26.2 abnormalities from MDS-SF3B1. Its TP53-mutated classification separates MDS with 0–9% blasts, generally requiring multihit TP53 abnormalities, from MDS/AML with 10–19% blasts, where any somatic TP53 mutation with variant allele frequency above 10% suffices. Thus, WHO MDS-biTP53 spans blast ranges that ICC divides between two entities. (pmc.ncbi.nlm.nih.gov)\n\nThe conventional 20% boundary is not universal for acute myeloid leukemia (AML). WHO removes a fixed minimum blast requirement for most AML-defining genetic abnormalities, including NPM1 mutation and RUNX1::RUNX1T1 fusion, while requiring clinicopathological correlation. ICC generally requires at least 10% blasts for these genetically defined AML entities; BCR::ABL1-positive AML retains a 20% threshold. Consequently, 10–19% blasts do not automatically mean MDS/AML. (pmc.ncbi.nlm.nih.gov)\n\nChildhood MDS has a separate WHO framework distinguishing low-blast disease from disease with increased blasts; ICC retains refractory cytopenia of childhood within its pediatric framework and does not apply MDS/AML below age 18. WHO places post-cytotoxic-therapy MDS among myeloid neoplasms secondary to cytotoxic treatment, whereas ICC appends “therapy-related” to the specific diagnosis. MDS/myeloproliferative neoplasms, including chronic myelomonocytic leukemia and SF3B1-associated disease with thrombocytosis, form a separate overlap group rather than adult MDS subtypes. (pmc.ncbi.nlm.nih.gov)"
    },
    {
      "heading": "Natural History and Prognostic Assessment",
      "text": "The course of MDS ranges from cytopenias that remain relatively stable for years to progressive bone marrow failure or transformation into acute myeloid leukemia (AML). Leukemic transformation is not inevitable, and death without AML does not necessarily indicate biologically stable disease: severe cytopenias can cause fatal infection or hemorrhage before transformation occurs. Overall survival and time to AML therefore measure different outcomes. The former includes deaths from any cause, whereas assessment of leukemic transformation must account for death without AML as a competing event. These distinctions are particularly important in older populations, in whom nonhematologic disease also contributes to mortality. (cancer.gov)\n\nThe International Prognostic Scoring System (IPSS), published by Peter Greenberg and colleagues in 1997, was developed from 816 patients with primary MDS. It combines three variables: marrow blast percentage, the number of peripheral-blood cytopenias, and cytogenetic risk. Cytopenias were defined as hemoglobin below 10 g/dL, platelets below \\(100 \\times 10^9/L\\), and absolute neutrophils below \\(1.8 \\times 10^9/L\\). The original cytogenetic groups were good, intermediate, and poor; normal karyotype and isolated del(5q), del(20q), or loss of the Y chromosome belonged to the good group, whereas chromosome 7 abnormalities and complex karyotypes were poor-risk findings. Weighted scores assign low, intermediate-1, intermediate-2, or high risk. These are prognostic strata, not diagnostic subtypes: morphologically similar cases can have different predicted outcomes. (ashpublications.org)\n\nGreenberg and colleagues’ revised system, IPSS-R, appeared in 2012 and used data from 7,012 patients with primary untreated MDS. It expanded cytogenetic classification to five groups—very good, good, intermediate, poor, and very poor—and scored the depth of anemia, thrombocytopenia, and neutropenia separately rather than simply counting affected lineages. It also separated marrow blast percentages of 2% or less from those above 2% but below 5%. Its five overall categories are very low, low, intermediate, high, and very high risk. Median overall survival in the development cohort was respectively 8.8, 5.3, 3.0, 1.6, and 0.8 years. These historical estimates describe the study population and its treatment context; they are not fixed life expectancies for patients receiving contemporary care. (pubmed.ncbi.nlm.nih.gov)\n\nThe Molecular International Prognostic Scoring System (IPSS-M), published by Elsa Bernard and colleagues in 2022, incorporates somatic mutations in 31 genes alongside hemoglobin, platelet count, marrow blast percentage, and IPSS-R cytogenetic category. Investigators developed it using pretreatment samples from 2,957 patients and validated it in an independent cohort of 754 Japanese patients. Its six categories are very low, low, moderate low, moderate high, high, and very high. Multihit TP53 alterations, FLT3 mutations, and KMT2A partial tandem duplication were strong adverse predictors; the favorable association of SF3B1 mutation depended on accompanying genetic alterations. Relative to IPSS-R, IPSS-M reassigned 46% of patients to a different risk category and improved discrimination of overall survival, leukemia-free survival, and leukemic transformation. (evidence.nejm.org)\n\nDisease-based scores do not capture all determinants of outcome. Functional status, age, cardiac or pulmonary disease, renal or hepatic impairment, and other cancers affect nonleukemic mortality and tolerance of treatment. Studies underlying the MDS-specific comorbidity index identified cardiac disease as both the most frequent comorbidity and the principal cause of nonleukemic death. Red-cell transfusion dependence provides additional prognostic information and is explicitly incorporated in the WHO-based Prognostic Scoring System. Blood counts, blast burden, transfusion requirements, and cytogenetic findings may change during follow-up, so a diagnosis-time estimate cannot describe the entire subsequent course. Moreover, treatment response changes the context in which baseline estimates apply. A cohort median identifies the time by which half a study population has died; it neither specifies an individual survival time nor eliminates the substantial variation within each risk category. (pubmed.ncbi.nlm.nih.gov)"
    },
    {
      "heading": "Supportive Care and Patient-Centered Outcomes",
      "text": "Red-cell transfusions temporarily replace deficient circulating erythrocytes, improving oxygen delivery and relieving symptoms of anemia, including breathlessness and fatigue. Platelet transfusions help control bleeding and may provide preventive support in settings of substantial bleeding risk. Neither intervention corrects the underlying abnormal marrow clone. Transfusion support therefore addresses clinically important consequences of MDS, whether used alone or alongside disease-directed treatment; it is active treatment rather than the absence of care. Its purposes include maintaining function and comfort, not simply changing laboratory values. (cancer.gov)\n\nRepeated exposure to donor cells can cause alloimmunization, in which antibodies develop against nonself blood-cell antigens. Red-cell antibodies complicate compatibility testing and can contribute to hemolytic transfusion reactions. A 2017 South Australian registry study reported an 11% cumulative incidence of red-cell alloimmunization; its development was associated with autoantibody formation and increased transfusion requirements. This observational association does not establish that antibodies alone caused the greater transfusion burden. Repeated red-cell transfusions also introduce iron that can accumulate in the liver, heart, and other organs, potentially impairing their function. (pmc.ncbi.nlm.nih.gov)\n\nIron-chelating drugs bind iron and facilitate its elimination. Deferoxamine and oral deferasirox are used in selected transfusion-dependent patients with iron overload, but reducing iron stores is not equivalent to demonstrating longer survival. In the 2020 TELESTO trial, Emanuele Angelucci and colleagues randomized 225 iron-overloaded patients with low- or intermediate-1-risk MDS to deferasirox or placebo. Median event-free survival was approximately 3.9 versus 3.0 years; the composite endpoint included cardiac or hepatic events, transformation to acute myeloid leukemia, and death. Interpretation is limited by the reduction of the planned study from phase III to phase II and its smaller enrollment target. Increased serum creatinine was more frequent with deferasirox, illustrating the importance of renal toxicity in the balance between benefit and treatment burden. (cancer.org)\n\nInfection management includes assessment and antimicrobial treatment of suspected or established infection. Evidence does not establish a general benefit from routine antibiotic prophylaxis in otherwise asymptomatic neutropenic MDS. Hematopoietic growth factors have distinct roles: erythropoiesis-stimulating agents can reduce anemia and transfusion requirements in responsive patients, whereas granulocyte colony-stimulating factor stimulates neutrophil production and is sometimes used when recurrent infections accompany low counts. Raising a cell count does not itself demonstrate fewer infections or improved survival, and routine preventive myeloid growth-factor treatment has not shown established benefit in asymptomatic neutropenic patients. (cancer.gov)\n\nPatient-centered assessment measures symptoms and daily functioning directly rather than inferring them solely from hemoglobin concentrations or transfusion frequency. Studies have used the FACIT-Fatigue scale and the EORTC QLQ-C30 to assess fatigue, physical functioning, and quality of life. The MDS-specific Quality of Life in Myelodysplasia Scale (QUALMS), prospectively validated in 2016, contains 38 questions: 33 core items and five optional items. Its international validation included 255 patients, with assessments at baseline and three to six months later. These instruments capture physical and emotional effects that blood-count responses alone cannot fully describe. (pubmed.ncbi.nlm.nih.gov)\n\nPalliative care can accompany transfusions and disease-directed treatment from diagnosis onward; it is not restricted to terminal illness or synonymous with hospice. Its scope includes symptom relief, psychological and social support, caregiver needs, and communication about treatment goals. Discussions may address the value patients place on symptom improvement, independence, and the burdens of continuing treatment. Specialist palliative services work alongside hematology care rather than requiring its withdrawal. (cancer.gov)"
    },
    {
      "heading": "Disease-Directed Medicines",
      "text": "Erythropoiesis-stimulating agents (ESAs), including epoetin alfa and darbepoetin alfa, activate erythropoietin receptors on erythroid progenitors, supporting their survival and proliferation. Their principal role in lower-risk MDS is improvement of anemia and reduction of red-cell transfusion requirements rather than eradication of the abnormal clone. Responses are more likely with lower endogenous erythropoietin concentrations and a smaller pre-existing transfusion burden. A rise in hemoglobin or reduced transfusion use does not itself establish remission or longer survival. (cancer.gov)\n\nLuspatercept promotes later-stage erythroid maturation. This fusion protein binds selected transforming growth factor-β superfamily ligands and reduces SMAD2/3 signaling, relieving signals that impede effective red-cell production. Its United States indications include anemia in ESA-naive adults with very-low- through intermediate-risk MDS who may require regular transfusions, and a separate indication after ESA failure in qualifying disease with ring sideroblasts. Hypertension is an important toxicity; fatigue, diarrhea, and musculoskeletal symptoms also occur. (accessdata.fda.gov) In the 2023 interim efficacy analysis of the phase III COMMANDS randomized trial, 58.5% of luspatercept recipients versus 31.2% of epoetin alfa recipients achieved at least 12 weeks of transfusion independence with a concurrent mean hemoglobin increase of at least 1.5 g/dL during weeks 1–24. These were erythroid-response endpoints, not evidence of a survival advantage. (pmc.ncbi.nlm.nih.gov)\n\nLenalidomide has a particularly defined role in transfusion-dependent, lower-risk MDS with deletion of chromosome 5q, including qualifying cases with additional cytogenetic abnormalities. It alters cereblon-dependent protein degradation, promoting destruction of casein kinase 1α; reduced expression of the gene encoding this protein in del(5q) cells helps explain their selective vulnerability. (cancer.gov) In a 148-patient phase II registration study, 67% achieved transfusion independence. Some patients also achieve cytogenetic responses, a distinct endpoint indicating reduction of the cytogenetically abnormal clone. Neutropenia and thrombocytopenia are major treatment-limiting toxicities. (cancer.gov)\n\nImetelstat is an oligonucleotide inhibitor of telomerase, the enzyme that maintains chromosome ends. On June 6, 2024, the United States Food and Drug Administration approved it for adults with IPSS low- or intermediate-1-risk MDS and transfusion-dependent anemia requiring at least four red-cell units over eight weeks, after inadequate response to, loss of response to, or ineligibility for ESAs. In the 178-patient, placebo-controlled IMerge trial, at least eight weeks of transfusion independence occurred in 39.8% with imetelstat versus 15.0% with placebo; corresponding rates for at least 24 weeks were 28.0% and 3.3%. Important toxicities include thrombocytopenia, neutropenia, and elevated liver enzymes. These results established a transfusion benefit, not a demonstrated survival benefit. (fda.gov)\n\nAzacitidine and decitabine are nucleoside analogues that inhibit DNA methyltransferases, reducing DNA methylation and altering gene expression; they also have cytotoxic effects. These hypomethylating treatments, used especially in higher-risk disease, are distinct from intensive acute-myeloid-leukemia-type chemotherapy. Myelosuppression and infection remain major hazards despite their lower-intensity schedules. (accessdata.fda.gov) In the 358-patient AZA-001 trial, published by Pierre Fenaux and colleagues in 2009, median overall survival was 24.5 months with azacitidine versus 15.0 months with conventional care. Comparable randomized evidence of prolonged survival has not been established for decitabine. (pmc.ncbi.nlm.nih.gov) Oral decitabine–cedazuridine combines decitabine with an inhibitor of cytidine deaminase, limiting its breakdown in the intestine and liver and enabling systemic exposure comparable to intravenous treatment; oral administration does not eliminate marrow toxicity. (accessdata.fda.gov)\n\nImmunosuppression with antithymocyte globulin, sometimes combined with cyclosporine, has a limited role in selected patients, particularly those with hypoplastic marrow and lower-risk disease; it is not a general treatment for all MDS. (cancer.gov) Licensed indications remain population- and jurisdiction-specific: efficacy within one defined subgroup does not establish efficacy across MDS, and investigational regimens require separate evaluation. Blood-count improvement, transfusion independence, marrow remission, and overall survival therefore remain distinct measures of benefit. (cancer.gov)"
    },
    {
      "heading": "Allogeneic Hematopoietic Stem Cell Transplantation",
      "text": "Allogeneic hematopoietic stem cell transplantation is an established treatment with curative potential in MDS. Preparative treatment, termed conditioning, suppresses the recipient’s immunity and reduces abnormal hematopoietic cells; infused donor stem cells then engraft in the bone marrow and establish donor-derived hematopoiesis. Donor immune cells also recognize and attack residual malignant cells through the graft-versus-leukemia effect. This combination of hematopoietic replacement and immune-mediated disease control can produce lasting eradication of the MDS clone, rather than merely improving circulating blood counts. Cure is not assured, because residual disease can survive conditioning or escape donor immune surveillance. (cancer.gov)\n\nTransplant assessment balances the anticipated course of untreated or medically treated MDS against transplantation-related risks. Disease variables include marrow blast percentage, cytogenetic abnormalities, molecular findings, prognostic risk category, and response to previous treatment. Recipient assessment includes performance status, frailty, and cardiac, pulmonary, hepatic, and renal function; the Hematopoietic Cell Transplantation–Specific Comorbidity Index helps quantify relevant comorbidity. Chronological age alone does not describe physiological fitness. Higher-risk disease generally creates greater urgency, whereas transplantation may be deferred in stable lower-risk disease until adverse evolution or clinically important marrow failure changes the balance. Donor selection considers human leukocyte antigen compatibility, donor age, and availability; matched siblings, unrelated volunteers, and partially matched relatives provide different donor options. (ncbi.nlm.nih.gov)\n\nConditioning intensity reflects the competing risks of relapse and treatment toxicity. Myeloablative regimens provide greater cytoreduction but impose substantial organ toxicity and marrow suppression. Reduced-intensity conditioning permits transplantation in some older or less physiologically fit patients and relies more heavily on donor immune activity. It does not eliminate serious complications. Long-term results of the randomized BMT CTN 0901 trial, which included both MDS and acute myeloid leukemia, illustrated the trade-off: reduced-intensity conditioning lowered treatment-related mortality but increased relapse relative to myeloablative conditioning. Because this was a mixed-disease population, its aggregate results are not MDS-specific outcome estimates. (pubmed.ncbi.nlm.nih.gov)\n\nEvidence for transplantation in selected older adults includes BMT CTN 1102, reported by Ryotaro Nakamura and colleagues in 2021. This prospective biological-assignment study enrolled 384 patients aged 50–75 years with intermediate-2 or high-risk de novo MDS at 34 centers during 2014–2018. Assignment depended on matched-donor availability rather than randomization. Adjusted three-year overall survival was 47.9% in the donor arm and 26.6% in the no-donor arm, an absolute difference of 21.3 percentage points. The comparison supported a survival benefit in this transplant-eligible study population, not an equivalent benefit for every older person with MDS. (pubmed.ncbi.nlm.nih.gov)\n\nRelapse and nonrelapse mortality are distinct competing outcomes: the latter denotes death without preceding disease recurrence. Important hazards include organ injury, infection, and graft-versus-host disease (GVHD). In GVHD, donor immune cells attack recipient tissues rather than malignant cells; acute disease commonly affects skin, intestine, and liver, while chronic disease can involve multiple organs and impair long-term functioning. Immunosuppressive treatment limits these reactions but also compromises antimicrobial defenses. In BMT CTN 1102 recipients transplanted within six months of assignment, treatment-related mortality at 27 months was 20.6% and relapse incidence was 29.6%, demonstrating that both pathways materially limited disease-free survival. (cancer.gov)\n\nGenetic findings further distinguish post-transplant risks. In a 2017 study led by R. Coleman Lindsley involving 1,514 recipients, TP53 mutations occurred in 19% and were associated with shorter survival and earlier relapse; myeloablative conditioning did not remove this adverse association. Separately, Matthew J. Duncavage and colleagues studied 90 adults in 2018: detection of a pre-existing somatic mutation at a variant allele frequency of at least 0.5% on day 30 was associated with one-year disease progression of 53.1%, compared with 13.0% without such persistence. These findings establish prognostic associations, rather than proving that a particular intervention triggered by mutation persistence improves survival. (nejm.org)"
    },
    {
      "heading": "Response Assessment and Research Directions",
      "text": "The International Working Group (IWG) criteria distinguish suppression of marrow disease from recovery of effective blood-cell production. The 2023 proposal for higher-risk MDS defines complete remission (CR) by bone marrow blasts below 5%, no circulating blasts, hemoglobin of at least 10 g/dL, platelets of at least \\(100 \\times 10^9/L\\), and an absolute neutrophil count of at least \\(1.0 \\times 10^9/L\\), with specified transfusion-independence requirements. Compared with IWG 2006, this lowered the hemoglobin threshold from 11 g/dL and changed the marrow-blast boundary from ≤5% to <5%. It also eliminated “marrow CR,” which could previously describe blast reduction without meaningful count recovery, and introduced provisional categories for CR with limited or partial hematologic recovery. Consequently, response rates calculated using IWG 2006 and IWG 2023 are not directly interchangeable. (ashpublications.org)\n\nHematologic improvement records erythroid, platelet, or neutrophil benefit without requiring CR. The IWG 2018 proposals, directed principally at lower-risk MDS, distinguish pretreatment transfusion burdens and assess erythroid responses against a documented baseline. For previously untransfused patients, an example is a sustained hemoglobin increase of at least 1.5 g/dL. Transfusion independence means receiving no transfusions of the specified component throughout a defined interval—not simply requiring fewer units. Studies must therefore identify their baseline requirements, observation window, and minimum response duration; an eight-week endpoint is not equivalent to a sixteen-week endpoint. Response duration measures persistence after response onset, whereas progression and relapse describe worsening disease or loss of an established response under version-specific rules. Transient treatment-induced cytopenias must not automatically be classified as progression. (pmc.ncbi.nlm.nih.gov)\n\nSerial assessment combines complete blood counts and transfusion records with marrow morphology, cytogenetics, and molecular measurements. These can reveal discordance between morphologic remission and persistence of an abnormal clone. In Eric Duncavage and colleagues’ 2018 study of 90 transplant recipients, persistence of at least one mutation at a variant allele frequency of 0.5% or greater on day 30 after transplantation was associated with a one-year progression risk of 53.1%, compared with 13.0% when no mutation met that threshold. Such findings support research into measurable residual disease and preemptive interventions. They do not establish mutation clearance as a validated surrogate for survival: a prognostic biomarker can identify risk without proving that treatment-induced alteration of that marker improves clinical outcomes. (pubmed.ncbi.nlm.nih.gov)\n\nResearch on treatment resistance includes molecularly selected populations whose disease has failed standard therapies. Courtney DiNardo and colleagues’ 2024 report evaluated the mutant-IDH1 inhibitor ivosidenib in a single-arm phase 1 substudy of relapsed or refractory IDH1-mutated MDS. Its design establishes safety and activity evidence, not a randomized estimate of survival benefit over another treatment. A separate mechanistic direction links altered RNA splicing to inflammatory signaling: Molly Smith and colleagues showed in 2019 that mutant U2AF1 promotes an exon-4-containing, long IRAK4 isoform that activates NF-κB signaling. IRAK4 inhibition impaired malignant-cell growth in experimental systems, providing a therapeutic rationale rather than proof of clinical benefit. (pubmed.ncbi.nlm.nih.gov)\n\nPredictive-model research also separates prognosis from treatment-response prediction. In a retrospective GenoMed4All validation involving 2,876 patients, the Molecular International Prognostic Scoring System improved concordance for overall survival from 0.74 with IPSS-R to 0.81 and reassigned 46% of patients to a different risk category. Nevertheless, it did not stratify the probability of response to hypomethylating agents in that analysis. This distinction makes treatment-specific prediction—rather than risk classification alone—an important target for subsequent model development and prospective clinical trials. (pubmed.ncbi.nlm.nih.gov)"
    }
  ],
  "links": [
    "cancer",
    "bone-marrow",
    "hematopoiesis",
    "leukemia",
    "world-health-organization",
    "anemia",
    "quality-of-life",
    "hematopoietic-stem-cell-transplantation",
    "cytogenetics",
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    "chemotherapy",
    "radiation-therapy",
    "dna-repair",
    "apoptosis",
    "rna-splicing",
    "epigenetics",
    "dna-methylation",
    "chromatin",
    "inflammation",
    "fatigue",
    "shortness-of-breath",
    "hemoglobin",
    "complete-blood-count",
    "neutrophil",
    "sepsis",
    "mean-corpuscular-volume",
    "biopsy",
    "dna-sequencing",
    "flow-cytometry",
    "vitamin-b12",
    "folate",
    "erythrocyte",
    "palliative-care",
    "randomized-controlled-trial",
    "major-histocompatibility-complex",
    "biomarker",
    "clinical-trial"
  ],
  "sources": [
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    },
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    {
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      "url": "https://seer.cancer.gov/archive/csr/1975_2017/browse_csr.php?pageSEL=sect_30_table.02&sectionSEL=30"
    },
    {
      "title": "Childhood Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version",
      "url": "https://www.cancer.gov/types/leukemia/patient/child-aml-treatment-pdq"
    },
    {
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      "url": "https://www.cancer.gov/types/myeloproliferative/patient/myelodysplastic-treatment-pdq"
    },
    {
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      "url": "https://www.cancer.gov/publications/pdq/information-summaries/genetics/hereditary-hematologic-malignancies"
    },
    {
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      "url": "https://pubmed.ncbi.nlm.nih.gov/23111193/"
    },
    {
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    },
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      "url": "https://www.cancer.gov/types/leukemia/hp/child-aml-treatment-pdq/myeloid-dysplastic-neoplasms-treatment-pdq"
    },
    {
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    },
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    },
    {
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    },
    {
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      "url": "https://pmc.ncbi.nlm.nih.gov/articles/8381722/"
    },
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    },
    {
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    },
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      "url": "https://pmc.ncbi.nlm.nih.gov/articles/pmid/35732831/"
    },
    {
      "title": "The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms",
      "url": "https://doi.org/10.1038/s41375-022-01613-1"
    },
    {
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      "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13229136/"
    },
    {
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      "url": "https://pubmed.ncbi.nlm.nih.gov/22740453/"
    },
    {
      "title": "Molecular International Prognostic Scoring System for Myelodysplastic Syndromes",
      "url": "https://pubmed.ncbi.nlm.nih.gov/38319256/"
    },
    {
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      "url": "https://pubmed.ncbi.nlm.nih.gov/21134982/"
    },
    {
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      "url": "https://pubmed.ncbi.nlm.nih.gov/16186598/"
    },
    {
      "title": "Supportive Therapy for Myelodysplastic Syndromes (MDS)",
      "url": "https://www.cancer.org/cancer/types/myelodysplastic-syndrome/treating/supportive-therapy.html"
    },
    {
      "title": "Red cell alloimmunization is associated with development of autoantibodies and increased red cell transfusion requirements in myelodysplastic syndrome",
      "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC5709101/"
    },
    {
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      "url": "https://www.immunology.ox.ac.uk/publications-legacy/1150697"
    },
    {
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    },
    {
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      "url": "https://pubmed.ncbi.nlm.nih.gov/25272332/"
    },
    {
      "title": "Prospective international validation of the Quality of Life in Myelodysplasia Scale (QUALMS)",
      "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC5013948/"
    },
    {
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    },
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      "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10428433/"
    },
    {
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      "url": "https://www.nature.com/articles/nature14610"
    },
    {
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    },
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    },
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    },
    {
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      "url": "https://www.cancer.gov/about-cancer/treatment/types/stem-cell-transplant"
    },
    {
      "title": "Myelodysplastic Neoplasms/Syndromes (MDS) - The EBMT Handbook",
      "url": "https://www.ncbi.nlm.nih.gov/books/NBK608269/"
    },
    {
      "title": "Donor Selection for Adults and Pediatrics - The EBMT Handbook",
      "url": "https://www.ncbi.nlm.nih.gov/books/NBK608270/"
    },
    {
      "title": "Myeloablative versus Reduced-Intensity Conditioning for Hematopoietic Cell Transplantation in Acute Myelogenous Leukemia and Myelodysplastic Syndromes—Long-Term Follow-Up of the BMT CTN 0901 Clinical Trial",
      "url": "https://pubmed.ncbi.nlm.nih.gov/33775615/"
    },
    {
      "title": "Biologic Assignment Trial of Reduced-Intensity Hematopoietic Cell Transplantation Based on Donor Availability in Patients 50-75 Years of Age With Advanced Myelodysplastic Syndrome",
      "url": "https://pubmed.ncbi.nlm.nih.gov/34106753/"
    },
    {
      "title": "Biologic Assignment Trial of Reduced-Intensity Hematopoietic Cell Transplantation Based on Donor Availability in Patients 50-75 Years of Age With Advanced Myelodysplastic Syndrome",
      "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8791814/"
    },
    {
      "title": "Proposals for revised IWG 2018 hematological response criteria in patients with MDS included in clinical trials",
      "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7042664/"
    },
    {
      "title": "Mutation Clearance after Transplantation for Myelodysplastic Syndrome",
      "url": "https://pubmed.ncbi.nlm.nih.gov/30207916/"
    },
    {
      "title": "Final phase 1 substudy results of ivosidenib for patients with mutant IDH1 relapsed/refractory myelodysplastic syndrome",
      "url": "https://pubmed.ncbi.nlm.nih.gov/38640348/"
    },
    {
      "title": "U2AF1 mutations induce oncogenic IRAK4 isoforms and activate innate immune pathways in myeloid malignancies",
      "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6679973/"
    },
    {
      "title": "Real-World Validation of Molecular International Prognostic Scoring System for Myelodysplastic Syndromes",
      "url": "https://pubmed.ncbi.nlm.nih.gov/36930857/"
    }
  ],
  "license": "https://creativecommons.org/licenses/by/4.0/"
}